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Revlimid (Lenalidomide) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Myelodysplastic Syndromes

A total of 148 patients received at least 1 dose of 10 mg lenalidomide in the del 5q MDS clinical study. At least one adverse event was reported in all of the 148 patients who were treated with the 10 mg starting dose of REVLIMID® (lenalidomide). The most frequently reported adverse events were related to blood and lymphatic system disorders, skin and subcutaneous tissue disorders, gastrointestinal disorders, and general disorders and administrative site conditions. (See PRECAUTIONS)

Thrombocytopenia (61.5%; 91/148) and neutropenia (58.8%; 87/148) were the most frequently reported adverse events observed. The next most common adverse events observed were diarrhea (48.6%; 72/148), pruritus (41.9%; 62/148), rash (35.8%; 53/148) and fatigue (31.1%; 46/148). Table 4 summarizes the adverse events that were reported in ≥ 5% of the REVLIMID® (lenalidomide) treated patients in the del 5q MDS clinical study. Table 5 summarizes the most frequently observed Grade 3 and Grade 4 adverse reactions regardless of relationship to treatment with REVLIMID® (lenalidomide). In the single-arm studies conducted, it is often not possible to distinguish adverse events that are drug-related and those that reflect the patient’s underlying disease.

Table 4: Summary of Adverse Events Reported in ≥ 5% of the REVLIMID® (lenalidomide) Treated Patients in del 5q MDS Clinical Study
NOS, not otherwise specified
[a] System organ classes and preferred terms are coded using the MedDRA dictionary. System organ classes and preferred terms are listed in descending order of frequency for the Overall column. A patient with multiple occurrences of an AE is counted only once in the AE category.
System organ class/Preferred term [a] 10 mg Overall
(N=148)
    Patients with at least one adverse event148(100.0)
Blood and Lymphatic System Disorders
    Thrombocytopenia91(61.5)
    Neutropenia87(58.8)
    Anemia NOS17(11.5)
    Leukopenia NOS12(8.1)
    Febrile Neutropenia8(5.4)
Skin and Subcutaneous Tissue Disorders
    Pruritus62(41.9)
    Rash NOS53(35.8)
    Dry Skin21(14.2)
    Contusion12(8.1)
    Night Sweats12(8.1)
    Sweating Increased10(6.8)
    Ecchymosis8(5.4)
    Erythema8(5.4)
Gastrointestinal Disorders
    Diarrhea NOS72(48.6)
    Constipation35(23.6)
    Nausea35(23.6)
    Abdominal Pain NOS18(12.2)
    Vomiting NOS15(10.1)
    Abdominal Pain Upper12(8.1)
    Dry Mouth10(6.8)
    Loose Stools9(6.1)
Respiratory, Thoracic and Mediastinal Disorders
    Nasopharyngitis34(23.0)
    Cough29(19.6)
    Dyspnea NOS25(16.9)
    Pharyngitis23(15.5)
    Epistaxis22(14.9)
    Dyspnea Exertional10(6.8)
    Rhinitis NOS10(6.8)
    Bronchitis NOS9(6.1)
General Disorders and Administration Site Conditions
    Fatigue46(31.1)
    Pyrexia31(20.9)
    Edema Peripheral30(20.3)
    Asthenia22(14.9)
    Edema NOS15(10.1)
    Pain NOS10(6.8)
    Rigors9(6.1)
    Chest Pain8(5.4)
Musculoskeletal and Connective Tissue Disorders
    Arthralgia32(21.6)
    Back Pain31(20.9)
    Muscle Cramp27(18.2)
    Pain in Limb16(10.8)
    Myalgia13(8.8)
    Peripheral Swelling12(8.1)
Nervous System Disorders
    Dizziness29(19.6)
    Headache29(19.6)
    Hypoesthesia10(6.8)
    Dysgeusia9(6.1)
    Peripheral Neuropathy NOS8(5.4)
Infections and Infestations
    Upper Respiratory Tract Infection NOS22(14.9)
    Pneumonia NOS17(11.5)
    Urinary Tract Infection NOS16(10.8)
    Sinusitis NOS12(8.1)
    Cellulitis8(5.4)
Metabolism and Nutrition Disorders
    Hypokalemia16(10.8)
    Anorexia15(10.1)
    Hypomagnesemia9(6.1)
Investigations
    Alanine Aminotransferase Increased12(8.1)
Psychiatric Disorders
    Insomnia15(10.1)
    Depression8(5.4)
Vascular Disorders
    Hypertension NOS9(6.1)
Renal and Urinary Disorders
    Dysuria10(6.8)
Cardiac Disorders
    Palpitations8(5.4)
Endocrine Disorders
    Acquired Hypothyroidism10(6.8)

Table 5: Most Frequently Observed Grade 3 and 4 Adverse Events [1] Regardless of Relationship to Study Drug Treatment
[1] Adverse events with frequency ≥1% in the 10 mg Overall group. Grade 3 and 4 are based on National Cancer Institute Common Toxicity Criteria version 2.
[2] Preferred Terms are coded using the MedDRA dictionary. A patient with multiple occurrences of an AE is counted only once in the Preferred Term category.
Preferred term [2] 10 mg
(N=148)
Patients with at least one Grade 3/4 AE131(88.5)
 Neutropenia79(53.4)
 Thrombocytopenia74(50.0)
 Pneumonia NOS11(7.4)
 Rash NOS10(6.8)
 Anemia NOS9(6.1)
 Leukopenia NOS8(5.4)
 Fatigue7(4.7)
 Dyspnea7(4.7)
 Back Pain7(4.7)
 Febrile Neutropenia6(4.1)
 Nausea6(4.1)
 Diarrhea NOS5(3.4)
 Pyrexia5(3.4)
 Sepsis4(2.7)
 Dizziness4(2.7)
 Granulocytopenia3(2.0)
 Chest Pain3(2.0)
 Pulmonary Embolism3(2.0)
 Respiratory Distress3(2.0)
 Pruritus3(2.0)
 Pancytopenia3(2.0)
 Muscle Cramp3(2.0)
 Respiratory Tract Infection2(1.4)
 Upper Respiratory Tract Infection2(1.4)
 Asthenia2(1.4)
 Multi-organ Failure2(1.4)
 Epistaxis2(1.4)
 Hypoxia2(1.4)
 Pleural Effusion2(1.4)
 Pneumonitis NOS2(1.4)
 Pulmonary Hypertension NOS2(1.4)
 Vomiting NOS2(1.4)
 Sweating Increased2(1.4)
 Arthralgia2(1.4)
 Pain in Limb2(1.4)
 Headache2(1.4)
 Syncope2(1.4)

In other clinical studies of REVLIMID® (lenalidomide) in MDS patients, the following serious adverse events (regardless of relationship to study drug treatment) not described in Table 4 or 5 were reported:

Blood and lymphatic system disorders: warm type hemolytic anemia, splenic infarction, bone marrow depression NOS, coagulopathy, hemolysis NOS, hemolytic anemia NOS, refractory anemia

Cardiac disorders: cardiac failure congestive, atrial fibrillation, angina pectoris, cardiac arrest, cardiac failure NOS, cardio-respiratory arrest, cardiomyopathy NOS, myocardial infarction, myocardial ischemia, atrial fibrillation aggravated, bradycardia NOS, cardiogenic shock, pulmonary edema NOS, supraventricular arrhythmia NOS, tachyarrhythmia, ventricular dysfunction

Ear and labyrinth disorders: vertigo

Endocrine disorders: Basedow’s disease

Gastrointestinal disorders: gastrointestinal hemorrhage NOS, colitis ischemic, intestinal perforation NOS, rectal hemorrhage, colonic polyp, diverticulitis NOS, dysphagia, gastritis NOS, gastroenteritis NOS, gastroesophageal reflux disease, obstructive inguinal hernia, irritable bowel syndrome, melena, pancreatitis due to biliary obstruction, pancreatitis NOS, perirectal abscess, small intestinal obstruction NOS, upper gastrointestinal hemorrhage

General disorders and administration site conditions: disease progression NOS, fall, gait abnormal, intermittent pyrexia, nodule, rigors, sudden death

Hepatobiliary disorders: hyperbilirubinemia, cholecystitis acute NOS, cholecystitis NOS, hepatic failure

Immune system disorders: hypersensitivity NOS

Infections and infestations: infection NOS, bacteremia, central line infection, clostridial infection NOS, ear infection NOS, Enterobacter sepsis, fungal infection NOS, herpes viral infection NOS, influenza, kidney infection NOS, Klebsiella sepsis, lobar pneumonia NOS, localized infection, oral infection, Pseudomonas infection NOS, septic shock, sinusitis acute NOS, sinusitis NOS, Staphylococcal infection, urosepsis

Injury, poisoning and procedural complications: femur fracture, transfusion reaction, cervical vertebral fracture, femoral neck fracture, fractured pelvis NOS, hip fracture, overdose NOS, post procedural hemorrhage, rib fracture, road traffic accident, spinal compression fracture

Investigations: blood creatinine increased, culture NOS negative, hemoglobin decreased, liver function tests NOS abnormal, troponin I increased

Metabolism and nutrition disorders: dehydration, gout, hypernatremia, hypoglycemia NOS

Musculoskeletal and connective tissue disorders: arthritis NOS, arthritis NOS aggravated, gouty arthritis, neck pain, chondrocalcinosis pyrophosphate

Neoplasms benign, malignant and unspecified: acute leukemia NOS, acute myeloid leukemia NOS, bronchoalveolar carcinoma, lung cancer metastatic, lymphoma NOS, prostate cancer metastatic

Nervous system disorders: cerebrovascular accident, aphasia, cerebellar infarction, cerebral infarction, depressed level of consciousness, dysarthria, migraine NOS, spinal cord compression NOS, subarachnoid hemorrhage NOS, transient ischemic attack

Psychiatric disorders: confusional state

Renal and urinary disorders: renal failure NOS, hematuria, renal failure acute, azotemia, calculus ureteric, renal mass NOS

Reproductive system and breast disorders: pelvic pain NOS

Respiratory, thoracic and mediastinal disorders: bronchitis NOS, chronic obstructive airways disease exacerbated, respiratory failure, dyspnea exacerbated, interstitial lung disease, lung infiltration NOS, wheezing

Skin and subcutaneous tissue disorders: acute febrile neutrophilic dermatosis

Vascular system disorders: deep vein thrombosis, hypotension NOS, aortic disorder, ischemia NOS, thrombophlebitis superficial, thrombosis

Multiple Myeloma

Data were evaluated from 691 patients in two studies who received at least one dose of REVLIMID® (lenalidomide)/dexamethasone (346 patients) or placebo/dexamethasone (345 patients).

In the REVLIMID® (lenalidomide)/dexamethasone treatment group, 151 patients (45%) underwent at least one dose interruption with or without a dose reduction of REVLIMID® (lenalidomide) compared to 21% in the placebo/dexamethasone treatment group. Of these patients who had one dose interruption with or without a dose reduction, 50% in the REVLIMID® (lenalidomide)/dexamethasone treatment group underwent at least one additional dose interruption with or without a dose reduction compared to 21% in the placebo/dexamethasone treatment group. Most adverse events and Grade 3/4 adverse events were more frequent in patients who received the combination of REVLIMID® (lenalidomide)/dexamethasone compared to placebo/dexamethasone.


Table 6 summarizes the number and percentage of patients with Grade 1-4 adverse events reported in ≥10% of patients in either treatment group in Studies 1 and 2.

Table 6: Number of Patients with Adverse Events Reported in at Least 10% of Patients  in Either Treatment Group in Studies 1 and 2 (Safety Population)
ª See WARNINGS
Revlimid/Dex
(N=346)
Placebo/Dex
(N=345)
System organ class/Preferred term n (%) n (%)
Subjects with at least one adverse event346(100.0)344(99.7)
Blood and Lymphatic System Disorders
 Neutropenia96(27.7)16(4.6)
 Anemia NOS84(24.3)60(17.4)
 Thrombocytopenia59(17.1)34(9.9)
Eye Disorders
 Vision Blurred51(14.7)36(10.4)
Gastrointestinal Disorders
 Constipation134(38.7)64(18.6)
 Diarrhea NOS101(29.2)85(24.6)
 Nausea76(22.0)66(19.1)
 Dyspepsia48(13.9)46(13.3)
 Vomiting NOS 35(10.1)28(8.1)
General Disorders and Administration Site Conditions
 Fatigue133(38.4)129(37.4)
 Asthenia81(23.4)86(24.9)
 Pyrexia80(23.1)67(19.4)
 Edema Peripheral73(21.1)65(18.8)
Infections and Infestations
 Upper Respiratory Tract Infection NOS47(13.6)43(12.5)
 Pneumonia NOS39(11.3)26(7.5)
Investigations
 Weight Decreased63(18.2)48(13.9)
Metabolism and Nutrition Disorders
 Hyperglycemia NOS52(15.0)49(14.2)
 Anorexia47(13.6)30(8.7)
 Hypokalemia39(11.3)18(5.2)
Musculoskeletal and Connective Tissue Disorders
 Muscle Cramp104(30.1)71(20.6)
 Back Pain53(15.3)49(14.2)
 Muscle Weakness NOS52(15.0)53(15.4)
 Arthralgia36(10.4)51(14.8)
Nervous System Disorders
 Headache74(21.4)74(21.4)
 Dizziness72(20.8)53(15.4)
 Tremor68(19.7)24(7.0)
 Dysgeusia46(13.3)32(9.3)
 Paresthesia40(11.6)43(12.5)
Psychiatric Disorders
 Insomnia111(32.1)128(37.1)
Respiratory, Thoracic and Mediastinal Disorders
 Dyspnea NOS70(20.2)53(15.4)
 Cough50(14.5)71(20.6)
Skin and Subcutaneous Tissue Disorders
 Rash NOS55(15.9)28(8.1)
Vascular Disorders
 Deep Vein Thrombosisa27(7.8)11(3.2)
 Pulmonary Embolisma11(3.2)3(0.9)

Table 7 summarizes the Grade 3/4 adverse events reported in ≥2% of patients in either treatment group in Studies 1 and 2.

Table 7: Adverse Events with NCI CTC Grades 3 and 4 Reported In At Least 2% of Patients by Preferred Term and Treatment Group – (Safety Population)
ª See WARNINGS
Revlimid/Dex (N=346) Placebo/Dex (N=345)
Grade 3 Grade 4 Grade 3 Grade 4
System organ class/ Preferred term n (%) n (%) n (%) n (%)
Patients with at least one Grade 3 or 4 AE225(65.0)25(7.2)186(53.9)31(9.0)
Blood and Lymphatic System Disorders
Neutropenia60(17.3)13(3.8)8(2.3)2(0.6)
Thrombocytopenia31(9.0)4(1.2)16(4.6)3(0.9)
Anemia NOS25(7.2)4(1.2)10(2.9)2(0.6)
Leukopenia NOS12(3.5)0(0.0)1(0.3)0(0.0)
Lymphopenia8(2.3)0(0.0)4(1.2)0(0.0)
Cardiac Disorders
Atrial Fibrillation9(2.6)1(0.3)2(0.6)1(0.3)
Gastrointestinal Disorders
Diarrhea NOS8(2.3)0(0.0)2(0.6)0(0.0)
Constipation7(2.0)0(0.0)1(0.3)0(0.0)
General Disorders and Administration Site Conditions
Fatigue20(5.8)1(0.3)13(3.8)0(0.0)
Asthenia14(4.0)0(0.0)16(4.6)0(0.0)
Pyrexia4(1.2)0(0.0)8(2.3)0(0.0)
Infections and Infestations
Pneumonia NOS18(5.2)4(1.2)15(4.3)3(0.9)
Metabolism and Nutrition Disorders
Hyperglycemia NOS22(6.4)4(1.2)19(5.5)7(2.0)
Hypocalcemia8(2.3)5(1.4)4(1.2)1(0.3)
Hypokalemia9(2.6)1(0.3)5(1.4)0(0.0)
Musculoskeletal and Connective Tissue Disorders
Muscle Weakness NOS18(5.2)0(0.0)10(2.9)0(0.0)
Nervous System Disorders
Syncope7(2.0)0(0.0)3(0.9)0(0.0)
Neuropathy NOS7(2.0)0(0.0)2(0.6)0(0.0)
Psychiatric Disorders
Depression9(2.6)0(0.0)5(1.4)1(0.3)
Confusional State6(1.7)0(0.0)8(2.3)0(0.0)
Respiratory, Thoracic and Mediastinal Disorders
Dyspnea NOS6(1.7)3(0.9)7(2.0)1(0.3)
Vascular Disorders
Deep Vein Thrombosisa23(6.6)1(0.3)9(2.6)1(0.3)
Pulmonary Embolisma2(0.6)9(2.6)1(0.3)2(0.6)

Thrombotic Events (See WARNINGS)

In the pooled analysis, thrombotic or thromboembolic events, including deep vein thrombosis, pulmonary embolism, thrombosis, and intracranial venous sinus thrombosis, were reported more frequently in patients treated with REVLIMID® (lenalidomide)/dexamethasone combination. The number of patients experiencing a thrombotic event in the combination arm were 43/346 (12%) compared with those in the placebo/dexamethasone arm 14/345 (4%).

In these and other clinical studies of REVLIMID® (lenalidomide) in patients with multiple myeloma, the following serious adverse events (considered related to study drug treatment) not described in Table 7 were reported:

Blood and lymphatic system disorders: pancytopenia, anemia NOS aggravated

Cardiac disorders: cardiac failure congestive, atrial flutter, pulmonary edema

Endocrine disorders: adrenal insufficiency NOS, acquired hypothyroidism

Eye disorders: blindness

Gastrointestinal disorders: abdominal pain NOS, colitis pseudomembranous, gastritis NOS, gastrointestinal hemorrhage NOS, peptic ulcer hemorrhage, upper gastrointestinal hemorrhage

General disorders and administration site conditions: performance status decreased

Hepatobiliary disorders: hepatic failure, hepatitis toxic

Infections and infestations: bronchopneumonia NOS, cellulitis, Pneumocystis carinii pneumonia, sepsis NOS, bursitis infective NOS, cellulitis staphylococcal, Enterobacter bacteremia, Escherichia sepsis, gastrointestinal infection NOS, herpes zoster, herpes zoster ophthalmic, infection NOS, lung infection NOS, neutropenic sepsis, pneumonia bacterial NOS, pneumonia cytomegaloviral, pneumonia pneumococcal, pneumonia primary atypical, pneumonia staphylococcal, septic shock, streptococcal sepsis, subacute endocarditis, urinary tract infection NOS

Investigations: International normalized ratio increased, weight decreased, blood creatinine increased, body temperature increased, c-reactive protein increased, hemoglobin decreased, white blood cell count decreased

Metabolism and nutrition disorders: dehydration, diabetes mellitus NOS, diabetes with hyperosmolarity, diabetic ketoacidosis

Musculoskeletal and connective tissue disorders: myopathy steroid, back pain, myopathy

Nervous system disorders: dizziness, memory impairment, brain edema, cerebral infarction, cerebral ischemia, cerebrovascular accident, encephalitis NOS, intracranial hemorrhage NOS, intracranial venous sinus thrombosis NOS, leukoencephalopathy, somnolence, tremor

Psychiatric disorders: mental status changes, delirium, delusion NOS, insomnia, psychotic disorder NOS

Renal and urinary disorders: Fanconi syndrome acquired, hematuria, renal failure acute, renal failure NOS, renal tubular necrosis, urinary retention

Respiratory, thoracic and mediastinal disorders: bronchopneumopathy, hypoxia

Skin and subcutaneous tissue disorders: rash NOS, skin desquamation NOS

Vascular system disorders: phlebitis NOS, venous thrombosis NOS limb, circulatory collapse, hypertension NOS, hypotension NOS, orthostatic hypotension, peripheral ischemia



REPORTS OF SUSPECTED REVLIMID SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Revlimid. The information is not vetted and should not be considered as verified clinical evidence.

Possible Revlimid side effects / adverse reactions in 96 year old female

Reported by a pharmacist from Italy on 2011-10-03

Patient: 96 year old female

Reactions: Death

Adverse event resulted in: death

Suspect drug(s):
Revlimid



Possible Revlimid side effects / adverse reactions in 71 year old male

Reported by a physician from Thailand on 2011-10-03

Patient: 71 year old male

Reactions: Lymphoma

Adverse event resulted in: death

Suspect drug(s):
Revlimid



Possible Revlimid side effects / adverse reactions in 59 year old male

Reported by a health professional (non-physician/pharmacist) from Germany on 2011-10-03

Patient: 59 year old male weighing 71.0 kg (156.2 pounds)

Reactions: Plasmacytoma, Pneumonia, Acute Myocardial Infarction

Adverse event resulted in: life threatening event, hospitalization

Suspect drug(s):
Dexamethasone
    Dosage: 40 milligram
    Indication: Multiple Myeloma
    Start date: 2011-07-01
    End date: 2011-07-22

Dexamethasone
    Start date: 2011-09-23

Revlimid
    Dosage: 25 milligram
    Administration route: Oral
    Indication: Multiple Myeloma
    Start date: 2011-07-01
    End date: 2011-07-21

Dexamethasone
    Dosage: 40 milligram
    Start date: 2011-07-29
    End date: 2011-08-05

Revlimid
    Dosage: 25 milligram
    Administration route: Oral
    Start date: 2011-07-29
    End date: 2011-08-11

Other drugs received by patient: Avelox; Avelox



See index of all Revlimid side effect reports >>

Drug label data at the top of this Page last updated: 2009-04-15

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